: Speech-sound disorders are the most prevalent group of speech/language disorders in children and comprise a complex group of disorders that have a heterogeneous underlying genetic basis. The long-term goal of the project is to identify genetic influences associated with speech-sound disorders that will result in the early identification and treatment of children at risk. Three specific aims will be addressed: (1) We will identify subgroups of sibling pairs with linkage to a chromosome region(s) by employing quantitative traits associated with speech sound production and oral and written language in order to clarify genotype-phenotype relationships and elucidate genetic factors that contribute to the overlap of speech sound, language, and reading disorders. We anticipate that these subgroups will refine our classification system of speech-sound disorders to produce new genetically and phenotypically meaningful categories. (2) Collection of multigenerational pedigrees of families will allow fine mapping of the susceptibility gene(s) and refinement of genetic transmission models, including testing for parent of origin effects. (3) We will measure longitudinal changes in the phenotype and identify genetic factors contributing to these changes. This project utilizes a large cohort of well characterized nuclear families of children with speech-sound disorders (N=250; DNA available N=164 families) from our previous family study. Longitudinal follow-up of probands and siblings from these nuclear families will be conducted to describe speech-sound, language, reading, and spelling outcomes associated with linkage to various chromosome regions and developmental changes in the phenotype. Extended family members of these families will be invited to participate in the study so that multigenerational pedigrees may be constructed. Model-free linkage and transmission disequilibrium tests will examine regions of chromosome 1, 3, 6, 7, 15, 16, and 19. Identification of subgroups of speech-sound disorders associated with different chromosome regions will result in more accurate diagnostic categories and improve our understanding of the relationship of speech sound disorders to reading disorders. Therapy may be tailored to address specific cognitive deficits associated with different genetic etiologies.